Role of the Electrogenic Na/K Pump in Disinhibition-Induced Bursting in Cultured Spinal Networks

Abstract

Darbon, P., A. Tscherter, C. Yvon, and J. Streit. Role of the electrogenic Na/K pump in disinhibition-induced bursting in cultured spinal networks. J Neurophysiol 90: 3119 -3129, 2003. First published July 30, 2003 10.1152/jn.00579.2003. Disinhibition-induced bursting activity in cultures of fetal rat spinal cord is mainly controlled by intrinsic spiking with subsequent recurrent excitation of the network through glutamate synaptic transmission, and by autoregulation of neuronal excitability. Here we investigated the contribution of the electrogenic Na/K pump to the autoregulation of excitability using extracellular recordings by multielectrode arrays (MEAs) and intracellular whole cell recordings from spinal interneurons. The blockade of the electrogenic Na/K pump by strophanthidin led to an immediate and transient increase in the burst rate together with an increase in the asynchronous background activity. Later, the burst rate decreased to initial values and the bursts became shorter and smaller. In single neurons, we observed an immediate depolarization of the membrane during the interburst intervals concomitant with the rise in burst rate. This depolarization was more pronounced during disinhibition than during control, suggesting that the pump was more active. Later a decrease in burst rate was observed and, in some neurons, a complete cessation of firing. Most of the effects of strophanthidin could be reproduced by high K ϩ -induced depolarization. During prolonged current injections, spinal interneurons exhibited spike frequency adaptation, which remained unaffected by strophanthidin. These results suggest that the electrogenic Na/K pump is responsible for the hyperpolarization and thus for the changes in excitability during the interburst intervals, although not for the spike frequency adaptation during the bursts.

Sodium and Calcium Current-Mediated Pacemaker Neurons and Respiratory Rhythm Generation

“…In the absence of I NaP and I CAN , we conclude that a compensatory boost in excitability depolarizes constituent neurons closer to spike threshold so that excitatory synaptic drive can still evoke the inspiratory burst without the amplification normally provided by I NaP and I CAN . We propose that inspiratory burst termination results from a collection of intrinsic cellular properties such as I NaP inactivation (Del Negro et al, 2002b;Rybak et al, 2003), I CAN deactivation, recruitment of calcium-dependent potassium channels, or electrogenic ion pumps (Ballerini et al, 1997;Darbon et al, 2003). These cellular processes can activate based on Na ϩ and Ca 2ϩ accumulation during inspiration.…”

The Persistent Sodium Current Generates Pacemaker Activities in the Central Pattern Generator for Locomotion and Regulates the Locomotor Rhythm

“…Thus, although additional investigations are needed to identify mechanisms for burst repolarization, regulation of the biophysical properties of I NaP seems to contribute (Butera et al, 1999;Del Negro et al, 2002). The Na ϩ /K ϩ electrogenic pump (Ballerini et al, 1997;Darbon et al, 2003), the Na ϩ -dependent K ϩ current (Schwindt et al, 1989), the glial KCl accumulation (Bikson et al, 1999), and slow activation of K ϩ currents (Yue and Yaari, 2004) might also regulate the burst repolarization process. It should be noted that the emergence of subthreshold oscillations in [Ca 2ϩ ] ofree ACSF unlikely results only from the modulation of I NaP because they were not induced by veratridine.…”

ERG Conductance Expression Modulates the Excitability of Ventral Horn GABAergic Interneurons That Control Rhythmic Oscillations in the Developing Mouse Spinal Cord

“…It is feasible to propose that, at this early stage, sustained firing of GABAergic neurons prolonged bursting and interburst firing. The slower period of bursting may be accounted for by the stronger coactivation of mechanisms like the Na ϩ -K ϩ pump (Ballerini et al 1997;Darbon et al, 2003), which usually restrains bursting frequency.…”